Fibrosis is a key hallmark of progressive chronic kidney disease (CKD) leading to kidney failure and is therefore an important therapeutic target. Now, Fan Yi and colleagues report that chimeric antigen receptor (CAR) T cells specific for extracellular matrix (ECM)-producing cells can attenuate fibrosis.

Having developed PDGFRβ-specific CAR T cells, the researchers adoptively transferred them into hypertensive mice at 1 and 2 weeks. Samples collected 4 weeks after DOCA/salt exposure showed improved glomerular filtration rate, urinary albumin-to-creatinine ratio, serum creatinine, blood urea nitrogen, blood pressure and kidney fibrosis in treated mice compared with controls. These improvements were accompanied by reductions in the kidney fibroblast, pericyte and myofibroblast populations, as well as a decrease in the tubulointerstitial levels of collagen I and vimentin. Injecting mice with CD5-targeted lipid nanoparticles for delivery of PDGFRβ CAR mRNA to T cells also protected against fibrosis in DOCA/salt mice. Moreover, in human kidney organoids exposed to cisplatin, microinjection of human PDGFRβ-specific CAR T cells reduced collagen accumulation.